Evaluation of Triple-Negative Breast Cancer Early Detection via Mammography Screening and Outcomes in African American and White American Patients.

This cohort study examines triple-negative breast cancer detection via mammography screening, treatment, and survival rates in African American and white American women.

Operational strategies in US cancer centers of excellence that support the successful accrual of racial and ethnic minorities in clinical trials.

Background: Study populations in clinical research must reflect US changing demographics, especially with the rise of precision medicine. However, racial and ethnic minority groups (REMGs) have low rates of participation in cancer clinical trials.

Methods: Criteria were developed to identify cancer centers able to accrue a higher than average proportion of REMGs into clinical trials.

Adjuvant endocrine therapy for breast cancer patients: impact of a health system outreach program to improve adherence.

Purpose: Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET.

Methods: We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (n = 4287) and after (n = 3580) implementation of the outreach program.

A Versatile Chemoenzymatic Synthesis for the Discovery of Potent Cryptophycin Analogs.

The cryptophycins are a family of macrocyclic depsipeptide natural products that display exceptionally potent antiproliferative activity against drug-resistant cancers. Unique challenges facing the synthesis and derivatization of this complex group of molecules motivated us to investigate a chemoenzymatic synthesis designed to access new analogs for biological evaluation. The cryptophycin thioesterase (CrpTE) and the cryptophycin epoxidase (CrpE) are a versatile set of enzymes that catalyze macrocyclization and epoxidation of over 20 natural cryptophycin metabolites.

Gleason score 5 + 3 = 8 (grade group 4) prostate cancer-a rare occurrence with contemporary grading.

Grade Group (GG) 4 prostate cancer includes Gleason scores (GS) 3 + 5 = 8, 4 + 4 = 8, and 5 + 3 = 8. Some studies without pathology re-review of historical cohorts proposed that the presence of pattern 5 worsens prognosis compared to GS 4 + 4 = 8 cancer. We assessed how often historically graded GS 5 + 3 = 8 cancers retain this grade with contemporary grading recommendations.

Evaluating Lung Cancer Screening Across Diverse Healthcare Systems: A Process Model from the Lung PROSPR Consortium.

Numerous organizations, including the United States Preventive Services Task Force, recommend annual lung cancer screening (LCS) with low-dose CT for high risk adults who meet specific criteria. Despite recommendations and national coverage for screening eligible adults through the Centers for Medicare and Medicaid Services, LCS uptake in the United States remains low (<4%). In recognition of the need to improve and understand LCS across the population, as part of the larger Population-based Research to Optimize the Screening PRocess (PROSPR) consortium, the NCI (Bethesda, MD) funded the Lung PROSPR Research Consortium consisting of five diverse healthcare systems in Colorado, Hawaii, Michigan, Pennsylvania, and Wisconsin.

Cardiac substructure segmentation with deep learning for improved cardiac sparing.

Purpose: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI's soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input.

Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations.

miR-183-96-182 Cluster Is Involved in Invariant NKT Cell Development, Maturation, and Effector Function.

The development, differentiation and function of invariant NKT (iNKT) cells require a well-defined set of transcription factors, but how these factors are integrated to each other and the detailed signaling networks remain poorly understood. Using a Dicer-deletion mouse model, our previous studies have demonstrated the critical involvement of microRNAs (miRNAs) in iNKT cell development and function, but the role played by individual miRNAs in iNKT cell development and function is still not clear. In this study, we show the dynamic changes of miRNA 183 cluster (miR-183C) expression during iNKT cell development.

Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma.

Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma.

Materials And Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy).

COPD-dependent effects of genetic variation in key inflammation pathway genes on lung cancer risk.

Genome-wide association studies (GWAS) have identified several loci contributing to lung cancer and COPD risk independently; however, inflammation-related pathways likely harbor additional lung cancer risk-associated variants in biologically relevant immune genes that differ dependent on COPD. We selected single nucleotide polymorphisms (SNPs) proximal to 2,069 genes within 48 immune pathways. We modeled the contribution of these variants to lung cancer risk in a discovery sample of 1,932 lung cancer cases and controls stratified by COPD status and validation sample of 953 cases and controls also stratified by COPD.

Modern Radiation Therapy Planning and Delivery.

Modern radiation therapy treatment planning and delivery is a complex process that relies on advanced imaging and computing technology as well as expertise from the medical team. The process begins with simulation imaging, in which three-dimensional computed tomography images (or magnetic resonance images in some cases) are used to characterize the patient anatomy. From there, the radiation oncologist delineates the relevant target/tumor volumes and normal tissue and communicates the goals for treatment planning.

The transformation of radiation oncology using real-time magnetic resonance guidance: A review.

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment.

Impact of CT reconstruction algorithm on auto-segmentation performance.

Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP).

The role of a low erythropoietin level for the polycythemia vera diagnosis.

A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). Controversies exist regarding the diagnostic value of a low EPO level when considering increasing availability of advanced molecular testing. We assessed the role of low EPO level for PV diagnosis in the context of positive JAK2 mutation status as well as other diagnostic parameters.

Executive Summary of the American Radium Society Appropriate Use Criteria for Local Excision in Rectal Cancer.

The goal of treatment for early stage rectal cancer is to optimize oncologic outcome while minimizing effect of treatment on quality of life. The standard of care treatment for most early rectal cancers is radical surgery alone. Given the morbidity associated with radical surgery, local excision for early rectal cancers has been explored as an alternative approach associated with lower rates of morbidity.

Renal cell tumors with an entrapped papillary component: a collision with predilection for oncocytic tumors.

Renal cell tumors with mixed morphology resembling multiple renal cell carcinoma (RCC) subtypes are generally regarded as unclassified RCC. However, occasionally, papillary adenoma or RCC appears admixed with a larger, different tumor histology. We retrieved 17 renal tumors containing a papillary adenoma or papillary RCC component admixed with another tumor histology and studied them with immunohistochemistry and fluorescence in situ hybridization (FISH).

Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative.

Objective: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations.

Background: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence.

Methods: We used a surgically maintained biospecimen cohort of 2884 BC cases.

Renal cell carcinomas with a mesenchymal stromal component: what do we know so far?

A subset of renal cell neoplasms contains a mesenchymal stromal component, often resembling smooth muscle. To date, it remains debated whether these represent one or more distinct pathological entities. The foremost of these, renal cell carcinoma with angioleiomyoma-like stroma (also known as smooth muscle or leiomyomatous stroma), has some distinctive features, including immunohistochemical positivity for cytokeratin 7 and often a lack of genetic changes of clear cell renal cell carcinoma.

Targeting prosurvival BCL2 signaling through Akt blockade sensitizes castration-resistant prostate cancer cells to enzalutamide.

Background: Prostate cancer that recurs after initial treatment inevitably progresses to castration-resistant prostate cancer (CRPC), the lethal stage of the disease. Despite improvements in outcomes from next generation androgen receptor (AR)-axis inhibitors, CRPC remains incurable. Therapeutic strategies to target AR antagonist resistance are urgently needed to improve outcomes for men with this lethal form of prostate cancer.

MYB-NFIB gene fusion in prostatic basal cell carcinoma: clinicopathologic correlates and comparison with basal cell adenoma and florid basal cell hyperplasia.

Prostatic basal cell carcinoma is a malignant neoplasm composed of basaloid cells forming infiltrative nests and tubules, which may potentially be misdiagnosed as benign basal cell proliferations (i.e., florid basal cell hyperplasia or basal cell adenoma) and also closely resembles adenoid cystic carcinoma of the salivary gland.

Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results.

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract.